Q99497 (PARK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein DJ-1
EC=3.4.-.-

Alternative name(s):
Oncogene DJ1
Parkinson disease protein 7

Gene names

Name:

PARK7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone. Ref.1 Ref.11 Ref.14 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.32 Ref.34
Subunit structure	Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF. Ref.11 Ref.12 Ref.14 Ref.22 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33
Subcellular location	Cytoplasm. Nucleus. Mitochondrion. Note: Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage. Detected in tau inclusions in brains from neurodegenerative disease patients. Ref.1 Ref.11 Ref.12 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.34 Ref.36
Tissue specificity	Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain. Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa. Ref.1 Ref.15 Ref.16 Ref.17
Induction	By hydrogen peroxide and UV irradiation. Ref.18 Ref.21
Post-translational modification	Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity. Ref.21 Cys-106 is easily oxidized to sulfinic acid. Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
Involvement in disease	Parkinson disease 7 (PARK7) [MIM:606324]: A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.35 Ref.36 Ref.38 Ref.39 Ref.40 Ref.43
Sequence similarities	Belongs to the peptidase C56 family.
Biophysicochemical properties	Kinetic parameters: KM=173.4 µM for casein Ref.26

Ontologies

Keywords
Biological process	Autophagy Fertilization Inflammatory response Stress response
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration Parkinson disease Parkinsonism Tumor suppressor
Ligand	RNA-binding
Molecular function	Chaperone Hydrolase Protease
PTM	Isopeptide bond Oxidation Phosphoprotein Ubl conjugation Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adult locomotory behavior Inferred from electronic annotation. Source: Compara autophagy Inferred from electronic annotation. Source: UniProtKB-KW cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular response to hydrogen peroxide Inferred from direct assay Ref.18. Source: UniProtKB dopamine uptake involved in synaptic transmission Inferred from electronic annotation. Source: Compara hydrogen peroxide metabolic process Inferred from electronic annotation. Source: Compara inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW membrane depolarization Inferred from electronic annotation. Source: Compara membrane hyperpolarization Inferred from electronic annotation. Source: Compara mitochondrion organization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of extrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 21785459. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from direct assay PubMed 22511790. Source: BHF-UCL negative regulation of protein binding Inferred from direct assay Ref.11. Source: UniProtKB positive regulation of oxidative phosphorylation uncoupler activity Inferred from electronic annotation. Source: Compara protein stabilization Inferred from mutant phenotype Ref.23. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of androgen receptor signaling pathway Inferred from direct assay Ref.11. Source: UniProtKB regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB single fertilization Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrion Inferred from direct assay Ref.25. Source: UniProtKB nucleus Inferred from direct assay Ref.11Ref.25. Source: UniProtKB
Molecular_function	mRNA binding Inferred from direct assay Ref.24. Source: UniProtKB peptidase activity Inferred from direct assay Ref.26. Source: UniProtKB peroxidase activity Inferred from sequence or structural similarity. Source: UniProtKB peroxiredoxin activity Inferred from electronic annotation. Source: Compara protein homodimerization activity Inferred from direct assay Ref.25. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	6	EBI-1164361,EBI-608057
DAXX	Q9UER7	3	EBI-1164361,EBI-77321
FADD	Q13158	9	EBI-1164361,EBI-494804
MTA2	O94776	3	EBI-1164361,EBI-1783035
OTUD7B	Q6GQQ9	3	EBI-1164361,EBI-527784

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – ?

Protein DJ-1

PRO_0000157849

Propeptide

? – 189

Removed in mature form

PRO_0000405558

Sites

Active site

106

1

Probable

Active site

126

1

Probable

Amino acid modifications

Modified residue

67

1

Phosphotyrosine Ref.20

Modified residue

106

1

Cysteine sulfinic acid (-SO2H)

Cross-link

130

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21

Natural variations

Natural variant

26

1

M → I in PARK7; does not affect protein stability and degradation; does not interfere with homodimerization. Ref.13 Ref.35

VAR_020492

Natural variant

64

1

E → D in PARK7; no apparent effect on protein stability; impaired mitochondrial morphology. Ref.38 Ref.39 Ref.44

VAR_020493

Natural variant

98

1

R → Q. Ref.35 Ref.37 Ref.40 Ref.41

VAR_020494

Natural variant

104

1

A → T in PARK7. Ref.40

VAR_020495

Natural variant

149

1

D → A in PARK7. Ref.35

VAR_020496

Natural variant

150

1

G → S. Ref.10

VAR_020497

Natural variant

163

1

E → K. Ref.42

VAR_034801

Natural variant

166

1

L → P in PARK7; reduces protein stability and leads to increased degradation; interferes with homodimerization; abolishes interaction with PIAS2; strongly reduces chaperone activity; ubiquitinated by PARK2, leading to its recognition by HDAC6 and targeting to aggresome where is degraded. Ref.12 Ref.13 Ref.36 Ref.39 Ref.43
Corresponds to variant rs28938172 [ dbSNP | Ensembl ].

VAR_020498

Natural variant

171

1

A → S. Ref.40

VAR_020499

Experimental info

Mutagenesis

46

1

C → A: Reduces protein stability. No effect on oxidation. Ref.19 Ref.25 Ref.34

Mutagenesis

46

1

C → S: No effect on mitochondrial translocation. Ref.19 Ref.25 Ref.34

Mutagenesis

51

1

V → A: Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide. Ref.18

Mutagenesis

53

1

C → A: Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide. Ref.18 Ref.19 Ref.25 Ref.34

Mutagenesis

53

1

C → S: No effect on mitochondrial translocation. Ref.18 Ref.19 Ref.25 Ref.34

Mutagenesis

106

1

C → A: Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduced binding to OTUD7B. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.34

Mutagenesis

106

1

C → D: Abolishes oxidation and association with mitochondria. No effect on chaperone activity. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.34

Mutagenesis

106

1

C → S: No effect on mitochondrial translocation. Reduced protease activity. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.34

Mutagenesis

126

1

H → A: Abolishes protease activity. Ref.26

Mutagenesis

130

1

K → R: Partially compensates for loss of stability; when associated with P-166. Ref.12

Sequence conflict

119

1

F → C in BAB71782. Ref.3

Secondary structure

1

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189

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Helix

16 – 28

13

Beta strand

32 – 37

6

Turn

38 – 41

4

Beta strand

51 – 53

3

Beta strand

55 – 57

3

Helix

58 – 62

5

Beta strand

68 – 72

5

Helix

76 – 84

9

Helix

86 – 97

12

Beta strand

101 – 105

5

Turn

106 – 108

3

Helix

109 – 114

6

Helix

127 – 129

3

Helix

130 – 133

4

Turn

134 – 136

3

Beta strand

139 – 141

3

Beta strand

145 – 149

5

Beta strand

152 – 155

4

Helix

158 – 160

3

Helix

161 – 173

13

Helix

175 – 182

8

Helix

183 – 185

3

Sequences

	Sequence		Length	Mass (Da)
	Q99497 [UniParc]. Last modified July 5, 2004. Version 2. Checksum: 4B21661B3A76BC67	FASTA	189	19,891
	10 20 30 40 50 60 MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV VICPDASLED 70 80 90 100 110 120 AKKEGPYDVV VLPGGNLGAQ NLSESAAVKE ILKEQENRKG LIAAICAGPT ALLAHEIGFG 130 140 150 160 170 180 SKVTTHPLAK DKMMNGGHYT YSENRVEKDG LILTSRGPGT SFEFALAIVE ALNGKEVAAQ VKAPLVLKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras." Nagakubo D., Taita T., Kitaura H., Ikeda M., Tamai K., Iguchi-Ariga S.M.M., Ariga H. Biochem. Biophys. Res. Commun. 231:509-513(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"Homo sapiens RNA-binding protein regulatory subunit mRNA." Beaudoin R., Hod Y. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[3]	"Human DJ-1 cDNA from PC3 cells." Ariga H., Niki T. Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix.
[8]	"Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter." Taira T., Takahashi K., Kitagawa R., Iguchi-Ariga S.M.M., Ariga H. Gene 263:285-292(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6. Tissue: Kidney.
[9]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 6-27; 33-89; 99-122 AND 149-175, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]	"DJ-1 gene G150S mutation." Zou H.Q., Chan P. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 138-189, VARIANT SER-150.
[11]	"DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor." Takahashi K., Taira T., Niki T., Seino C., Iguchi-Ariga S.M.M., Ariga H. J. Biol. Chem. 276:37556-37563(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIAS2, SUBCELLULAR LOCATION, FUNCTION.
[12]	"L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system." Miller D.W., Ahmad R., Hague S., Baptista M.J., Canet-Aviles R., McLendon C., Carter D.M., Zhu P.-P., Stadler J., Chandran J., Klinefelter G.R., Blackstone C., Cookson M.R. J. Biol. Chem. 278:36588-36595(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DEGRADATION BY THE PROTEASOME, SUBCELLULAR LOCATION, INTERACTION WITH PIAS2, HOMODIMERIZATION, MUTAGENESIS OF LYS-130, CHARACTERIZATION OF VARIANT PARK7 PRO-166.
[13]	"A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization." Moore D.J., Zhang L., Dawson T.M., Dawson V.L. J. Neurochem. 87:1558-1567(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DEGRADATION BY THE PROTEASOME, CHARACTERIZATION OF VARIANTS PARK7 ILE-26 AND PRO-166.
[14]	"DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex." Niki T., Takahashi-Niki K., Taira T., Iguchi-Ariga S.M.M., Ariga H. Mol. Cancer Res. 1:247-261(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EFCAB6, FUNCTION.
[15]	"Immunocytochemical localization of DJ-1 in human male reproductive tissue." Yoshida K., Sato Y., Yoshiike M., Nozawa S., Ariga H., Iwamoto T. Mol. Reprod. Dev. 66:391-397(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[16]	"DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia." Rizzu P., Hinkle D.A., Zhukareva V., Bonifati V., Severijnen L.-A., Martinez D., Ravid R., Kamphorst W., Eberwine J.H., Lee V.M.-Y., Trojanowski J.Q., Heutink P. Ann. Neurol. 55:113-118(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[17]	"The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease." Bandopadhyay R., Kingsbury A.E., Cookson M.R., Reid A.R., Evans I.M., Hope A.D., Pittman A.M., Lashley T., Canet-Aviles R., Miller D.W., McLendon C., Strand C., Leonard A.J., Abou-Sleiman P.M., Healy D.G., Ariga H., Wood N.W., de Silva R. , Revesz T., Hardy J.A., Lees A.J. Brain 127:420-430(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[18]	"DJ-1 has a role in antioxidative stress to prevent cell death." Taira T., Saito Y., Niki T., Iguchi-Ariga S.M., Takahashi K., Ariga H. EMBO Rep. 5:213-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, MUTAGENESIS OF VAL-51 AND CYS-53.
[19]	"DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation." Shendelman S., Jonason A., Martinat C., Leete T., Abeliovich A. PLoS Biol. 2:1-10(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106.
[20]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-67, MASS SPECTROMETRY.
[21]	"Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities." Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C., Seino C., Iguchi-Ariga S.M.M., Ariga H. Cell Death Differ. 13:96-108(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-130, OXIDATION, SUBCELLULAR LOCATION, INDUCTION, FUNCTION.
[22]	"DJ-1 interacts with HIPK1 and affects H2O2-induced cell death." Sekito A., Koide-Yoshida S., Niki T., Taira T., Iguchi-Ariga S.M.M., Ariga H. Free Radic. Res. 40:155-165(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HIPK1, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-106.
[23]	"DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2." Clements C.M., McNally R.S., Conti B.J., Mak T.W., Ting J.P. Proc. Natl. Acad. Sci. U.S.A. 103:15091-15096(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[24]	"RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways." van der Brug M.P., Blackinton J., Chandran J., Hao L.Y., Lal A., Mazan-Mamczarz K., Martindale J., Xie C., Ahmad R., Thomas K.J., Beilina A., Gibbs J.R., Ding J., Myers A.J., Zhan M., Cai H., Bonini N.M., Gorospe M., Cookson M.R. Proc. Natl. Acad. Sci. U.S.A. 105:10244-10249(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[25]	"Mitochondrial localization of DJ-1 leads to enhanced neuroprotection." Junn E., Jang W.H., Zhao X., Jeong B.S., Mouradian M.M. J. Neurosci. Res. 87:123-129(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106.
[26]	"Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage." Chen J., Li L., Chin L.S. Hum. Mol. Genet. 19:2395-2408(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITES, MUTAGENESIS OF CYS-106 AND HIS-126.
[27]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"DJ-1 enhances cell survival through the binding of cezanne, a negative regulator of NF-{kappa}B." McNally R.S., Davis B.K., Clements C.M., Accavitti-Loper M.A., Mak T.W., Ting J.P. J. Biol. Chem. 286:4098-4106(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BBS1; CLCF1; MTERF AND OTUD7B, MUTAGENESIS OF CYS-106.
[29]	"Crystal structure of DJ-1/RS and implication on familial Parkinson's disease." Huai Q., Sun Y., Wang H., Chin L.-S., Li L., Robinson H., Ke H. FEBS Lett. 549:171-175(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), HOMODIMERIZATION.
[30]	"Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease." Tao X., Tong L. J. Biol. Chem. 278:31372-31379(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF WILD-TYPE AND MUTANT ARG-130, HOMODIMERIZATION.
[31]	"The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease." Honbou K., Suzuki N.N., Horiuchi M., Niki T., Taira T., Ariga H., Inagaki F. J. Biol. Chem. 278:31380-31384(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS), HOMODIMERIZATION.
[32]	"Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain." Lee S.-J., Kim S.J., Kim I.-K., Ko J., Jeong C.-S., Kim G.-H., Park C., Kang S.-O., Suh P.-G., Lee H.-S., Cha S.-S. J. Biol. Chem. 278:44552-44559(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), FUNCTION, OXIDATION, HOMODIMERIZATION.
[33]	"The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease." Wilson M.A., Collins J.L., Hod Y., Ringe D., Petsko G.A. Proc. Natl. Acad. Sci. U.S.A. 100:9256-9261(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS), HOMODIMERIZATION, OXIDATION, LACK OF PROTEOLYTIC ACTIVITY.
[34]	"The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization." Canet-Aviles R.M., Wilson M.A., Miller D.W., Ahmad R., McLendon C., Bandyopadhyay S., Baptista M.J., Ringe D., Petsko G.A., Cookson M.R. Proc. Natl. Acad. Sci. U.S.A. 101:9103-9108(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS), MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106, OXIDATION, FUNCTION, SUBCELLULAR LOCATION.
[35]	"The role of pathogenic DJ-1 mutations in Parkinson's disease." Abou-Sleiman P.M., Healy D.G., Quinn N., Lees A.J., Wood N.W. Ann. Neurol. 54:283-286(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PARK7 ILE-26 AND ALA-149, VARIANT GLN-98.
[36]	"Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism." Bonifati V., Rizzu P., van Baren M.J., Schaap O., Breedveld G.J., Krieger E., Dekker M.C.J., Squitieri F., Ibanez P., Joosse M., van Dongen J.W., Vanacore N., van Swieten J.C., Brice A., Meco G., van Duijn C.M., Oostra B.A., Heutink P. Science 299:256-259(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK7 PRO-166, SUBCELLULAR LOCATION.
[37]	"The R98Q variation in DJ-1 represents a rare polymorphism." Hedrich K., Schaefer N., Hering R., Hagenah J., Lanthaler A.J., Schwinger E., Kramer P.L., Ozelius L.J., Bressman S.B., Abbruzzese G., Martinelli P., Kostic V., Pramstaller P.P., Vieregge P., Riess O., Klein C. Ann. Neurol. 55:145-146(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-98.
[38]	"Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7)." Hering R., Strauss K.M., Tao X., Bauer A., Woitalla D., Mietz E.M., Petrovic S., Bauer P., Schaible W., Mueller T., Schoels L., Klein C., Berg D., Meyer P.T., Schulz J.B., Wollnik B., Tong L., Krueger R., Riess O. Hum. Mutat. 24:321-329(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK7 ASP-64, X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[39]	"Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1." Goerner K., Holtorf E., Odoy S., Nuscher B., Yamamoto A., Regula J.T., Beyer K., Haass C., Kahle P.J. J. Biol. Chem. 279:6943-6951(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PARK7 ASP-64 AND PRO-166.
[40]	"Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations." Clark L.N., Afridi S., Mejia-Santana H., Harris J., Louis E.D., Cote L.J., Andrews H., Singleton A., Wavrant De-Vrieze F., Hardy J., Mayeux R., Fahn S., Waters C., Ford B., Frucht S., Ottman R., Marder K. Mov. Disord. 19:796-800(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK7 THR-104, VARIANTS GLN-98 AND SER-171.
[41]	"DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease." Hedrich K., Djarmati A., Schafer N., Hering R., Wellenbrock C., Weiss P.H., Hilker R., Vieregge P., Ozelius L.J., Heutink P., Bonifati V., Schwinger E., Lang A.E., Noth J., Bressman S.B., Pramstaller P.P., Riess O., Klein C. Neurology 62:389-394(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-98.
[42]	"DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex." Annesi G., Savettieri G., Pugliese P., D'Amelio M., Tarantino P., Ragonese P., La Bella V., Piccoli T., Civitelli D., Annesi F., Fierro B., Piccoli F., Arabia G., Caracciolo M., Ciro Candiano I.C., Quattrone A. Ann. Neurol. 58:803-807(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LYS-163.
[43]	"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6." Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S. J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT PARK7 PRO-166.
[44]	"Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1." Krebiehl G., Ruckerbauer S., Burbulla L.F., Kieper N., Maurer B., Waak J., Wolburg H., Gizatullina Z., Gellerich F.N., Woitalla D., Riess O., Kahle P.J., Proikas-Cezanne T., Kruger R. PLoS ONE 5:E9367-E9367(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASP-64.
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D61380 mRNA. Translation: BAA09603.2.
AF021819 mRNA. Translation: AAC12806.1.
AB073864 mRNA. Translation: BAB71782.1.
AK312000 mRNA. Translation: BAG34938.1.
AL034417 Genomic DNA. Translation: CAB52550.1.
CH471130 Genomic DNA. Translation: EAW71591.1.
BC008188 mRNA. Translation: AAH08188.1.
AB045294 Genomic DNA. No translation available.
AY648999 Genomic DNA. Translation: AAT68961.1.

IPI

IPI00298547.

PIR

JC5394.

RefSeq

NP_001116849.1. NM_001123377.1.
NP_009193.2. NM_007262.4.

UniGene

Hs.419640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J42	X-ray	2.50	A	1-189	[»]
1P5F	X-ray	1.10	A	1-189	[»]
1PDV	X-ray	1.80	A	1-189	[»]
1PDW	X-ray	2.20	A/B/C/D/E/F/G/H	1-189	[»]
1PE0	X-ray	1.70	A/B	1-189	[»]
1Q2U	X-ray	1.60	A	1-189	[»]
1SOA	X-ray	1.20	A	1-189	[»]
1UCF	X-ray	1.95	A/B	1-189	[»]
2OR3	X-ray	1.20	A/B	1-189	[»]
2R1T	X-ray	1.70	A/B	2-188	[»]
2R1U	X-ray	1.50	A/B	2-188	[»]
2R1V	X-ray	1.70	A/B	2-188	[»]
2RK3	X-ray	1.05	A	1-189	[»]
2RK4	X-ray	1.15	A	1-189	[»]
2RK6	X-ray	1.15	A	1-189	[»]
3B36	X-ray	1.50	A	1-189	[»]
3B38	X-ray	1.85	A	1-189	[»]
3B3A	X-ray	1.50	A	1-189	[»]
3BWE	X-ray	2.40	A/B/C/D/E/F/G	1-189	[»]
3CY6	X-ray	1.35	A	1-189	[»]
3CYF	X-ray	1.60	A	1-189	[»]
3CZ9	X-ray	1.15	A	1-189	[»]
3CZA	X-ray	1.20	A	1-189	[»]
3EZG	X-ray	1.15	A	1-189	[»]
3F71	X-ray	1.20	A	1-189	[»]
3SF8	X-ray	1.56	A/B	1-189	[»]

ProteinModelPortal

Q99497.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35515N.

IntAct

Q99497. 28 interactions.

STRING

9606.ENSP00000340278.

Protein family/group databases

MEROPS

C56.002.

PTM databases

PhosphoSite

Q99497.

Polymorphism databases

DMDM

56404943.

2D gel databases

OGP

Q99497.

REPRODUCTION-2DPAGE

IPI00298547.

UCD-2DPAGE

O14805.
Q99497.

Proteomic databases

PaxDb

Q99497.

PeptideAtlas

Q99497.

PRIDE

Q99497.

Protocols and materials databases

DNASU

11315.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338639; ENSP00000340278; ENSG00000116288.
ENST00000377488; ENSP00000366708; ENSG00000116288.
ENST00000377491; ENSP00000366711; ENSG00000116288.
ENST00000493373; ENSP00000465404; ENSG00000116288.
ENST00000493678; ENSP00000418770; ENSG00000116288.

GeneID

11315.

KEGG

hsa:11315.

UCSC

uc001aou.4. human.

Organism-specific databases

CTD

11315.

GeneCards

GC01P007944.

HGNC

HGNC:16369. PARK7.

HPA

CAB005870.
HPA004190.

MIM

168600. phenotype.
602533. gene.
606324. phenotype.

neXtProt

NX_Q99497.

Orphanet

90020. Amyotrophic lateral sclerosis-parkinsonism-dementia complex.
2828. Young adult-onset Parkinsonism.

PharmGKB

PA32946.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0693.

HOGENOM

HOG000063194.

HOVERGEN

HBG053511.

InParanoid

Q99497.

KO

K05687.

OMA

GDHYKYS.

OrthoDB

EOG4DJJXJ.

PhylomeDB

Q99497.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.

Gene expression databases

Bgee

Q99497.

CleanEx

HS_PARK7.

Genevestigator

Q99497.

Family and domain databases

InterPro

IPR006287. DJ1.
IPR002818. ThiJ/PfpI.
[Graphical view]

Pfam

PF01965. DJ-1_PfpI. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01383. not_thiJ. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q99497.

GenomeRNAi

11315.

NextBio

42983.

PMAP-CutDB

Q99497.

SOURCE

Search...

Entry information

Entry name

PARK7_HUMAN

Accession

Primary (citable) accession number: Q99497
Secondary accession number(s): B2R4Z1 , O14805, Q6DR95, Q7LFU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.